OVERALL PROJECT SUMMARY ABSTRACT Funds are requested to renew a Center of Biomedical Research Excellence (COBRE) at the University of Kansas Medical Center (KUMC) as a Phase III, five year award. This COBRE has a research focus on the regulation of cell development and differentiation, which may provide new, therapeutic insights into a host of developmental abnormalities and diseases. During the initial 10 year term, we will have trained 15 Beginning Investigators and most of them are becoming successful, independent researchers. An important feature of this application is the maintenance of 3 scientific Cores that provide research support to all of the Center faculty as well as to KUMC as a whole. Together with Administrative Core A, there are Cores supporting transgenesis in mice and rats (Core B), molecular profiling (next generation sequencing, microarray, and bioinformatics, Core C), and high resolution imaging (confocal and electron microscopy, Core D). The second major component of this application is the operation of a Pilot Projects Program in developmental biology, which represents a natural extension of a pilot program initiated in Phase I and II that has a proven, successful track record. The outstanding combination of scientific talent, strong research environment, and substantial institutional commitment to the scientific Cores and Pilot Projects Program ensure that this COBRE will continue to foster the development of a thematic, multidisciplinary research effort and enhance the ability of KUMC researchers to compete for extramural support.